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Basic Methods
Published in Josef Hladovec, Antithrombotic Drugs in Thrombosis Models, 2020
While induction of a vascular lesion is relatively easy, it is much more difficult to demonstrate its presence. The necessity of a quantitative method for the estimation of circulating endothelial cells was obvious at first sight. Such a method would represent a direct indicator of a vascular lesion avoiding morphological examination of the vessel wall. Meanwhile, it has been shown using morphological methods, that a certain degree of vascular lesions is invariably associated with the desquamation of endothelial cells leaving behind typical endothelial defects. Theoretically, it might be possible to show in blood the presence of various constituents of endothelial lining, e.g., components of the surface coat and other materials released from damaged endothelial cells. On the other hand, very similar materials are present mostly in all formed blood elements and tissue cells and many constituents of endothelial cells may be present in blood even under physiological conditions. To demonstrate cells or their formed remnants would represent a much more direct and specific proof of a vascular lesion.
Programmed Aging Paradigm and Aging of Perennial Neurons
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
For the following discussion, endothelial cells will be used as an important example of nonneuronal cells that undergo turnover. Risk factors for cardiovascular diseases, such as age, diabetes, smoking, body mass index (i.e., overweight and obesity), and hypertension (Wilson et al. 1987), are associated with a reduced number of endothelial progenitor cells (Hill et al. 2003), likely caused by a quicker turnover of endothelial cells: “continuous endothelial damage or dysfunction leads to an eventual depletion or exhaustion of a presumed finite supply of endothelial progenitor cells … continuous risk-factor-induced injury may lead to eventual depletion of circulating endothelial cells” (Hill et al. 2003). This would be analogous to what happens in patients with muscular dystrophy, where there is an exhaustion of skeletal muscle stem cells (Webster and Blau 1990, Decary et al. 2000, Seale et al. 2001) as well as in a number of age-related conditions (Tyner et al. 2002, Geiger and Van Zant 2002).
Optimum Biological Dose Selection
Published in Atanu Bhattacharjee, Bayesian Approaches in Oncology Using R and OpenBUGS, 2020
Establishing a biomarker for cancer is a difficult task. Unless biomarker is established, it is challenging to establish the best effective metronomic dose. We will illustrate the methodology with simulated data. A simulation study was carried to explore the OBD and check the MC performance. The skewed distribution was used to obtain the head and neck cancer (HNC) data. The circulating endothelial cell (CEC) is considered as a biomarker. The repeatedly measured CEC is controlled within the desired level or not is considered as an outcome of dose. The prior mean 114 and standard deviation 15 are considered to generated CEC measurement. A total of 4 doses named as dose 1, dose 2 dose 3 and dose 4 are presented. Data is generated for a total of 220 patients. Persons alive status is presented as 0 or 1. the solid tumor size is generated from (mean 4.0 cm, SD 2). histological grading is measured as ( well, moderate and poor)were generated randomly for a total of 220 patients and merged with the excel sheet. The survival representation is provided by the Kaplan-Meier curve on progression-free survival in Figure 5.4. Relapse is considered an event. A total of five follow-up visits observations for CEC and tumor size were assumed to be distributed with a normal distribution. Different time points are assumed as t1, t2, t3, t4, t5. Corresponding mean of CEC is assumed as 124, 128, 135, 126, and 120 respectively. Censored distribution about duration of survival was obtained from a hazard rate of 0.0003 with approximately 45% censored observations.
Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients
Published in Biomarkers, 2023
Marie de Bakker, Jaco Kraan, K. Martijn Akkerhuis, Rohit Oemrawsingh, Folkert W. Asselbergs, Imo Hoefer, Isabella Kardys, Eric Boersma
Circulating endothelial cells (CEC) are present in the peripheral blood and represent mature endothelial cells, that have detached from vessel walls at sites of vascular injury, often as result of ischaemic disease (Kachamakova-Trojanowska et al.2015). Because of their close relationship with vascular injury (Kachamakova-Trojanowska et al.2015), CECs may provide a window into the pathophysiologic, vulnerable state preceding an ACS event and carry potential to improve individual risk assessment (Schmidt et al.2015). To date, two prospective studies in patients with ACS have demonstrated associations between baseline CEC count and incident cardiovascular events (Lee et al.2005, Boos et al.2008). Nonetheless, distinguishing patients at different levels of risk of adverse events based on a single baseline measurement is challenging. Longitudinal profiles of CECs may improve personalised risk assessment and could ultimately aid in the timing of treatment. However, studies on repeated CEC measurements and the temporal evolution of CEC preceding a recurrent event are lacking.
Transplant-associated thrombotic microangiopathy: elucidating prevention strategies and identifying high-risk patients
Published in Expert Review of Hematology, 2021
Sonata Jodele, Anthony Sabulski
A cellular marker of endothelial injury after HSCT has also been identified and is highly relevant to TA-TMA. Initial endothelial injury from conditioning chemotherapy, radiation, viremia, sepsis or other instigators results in direct endothelial damage. This permanently injures endothelial cells and releases them into the circulation. These cells are then termed circulating endothelial cells (CECs). CECs can be isolated from the blood and either quantified or directly studied as a liquid biopsy of the vascular wall. Woywodt et al. studied CECs in allogeneic HSCT recipients and found that CECs were elevated from baseline after HSCT and the kinetics of their elevations were dependent on preparative regimens [54]. Since then there have been multiple additional studies investigating CECs in HSCT recipients, though much of the focus has surrounded their potential use in GvHD [55–57]. Limited data exist on CECs in TA-TMA, however multiple studies have shown that CECs are elevated in non-HSCT TMA patients prior to therapy, and decrease in number after successful treatment [58,59]. Emerging data on CECs in TA-TMA patients were presented by Sabulski et al. at the 2021 Transplantation and Cellular Therapy meeting. Data from their prospective longitudinal study showed that all patients with high-risk TA-TMA or TA-TMA requiring eculizumab therapy more than doubled their baseline CEC count after HSCT [60,61]. The same group showed that CECs can be examined using transmission electron microscopy, which highlights the potential use of these cells as a noninvasive endothelial biopsy [62].
Ramucirumab: the long and winding road toward being an option for mCRC treatment
Published in Expert Opinion on Biological Therapy, 2019
Celine Debeuckelaere, Sabina Murgioni, Sara Lonardi, Noemi Girardi, Giulia Alberti, Carolina Fano, Sara Gallimberti, Cristina Magro, Selma Ahcene-Djaballah, Francesca Daniel, Matteo Fassan, Hans Prenen, Fotios Loupakis
Other possible biomarkers tested in bevacizumab-treated patients are circulating endothelial cells (CECs) and circulating endothelial cell progenitors (CEPs). Willet et al. observed that blood concentration of CECs decreased on day 12 after the administration of bevacizumab [31] and subsequently other studies confirmed the suppression of CECs and CEPs by antiangiogenic treatments [32]. Furthermore, preclinical studies showed a dose-dependent reduction of viable CEPs after treatment with VEGFR-2 antibody in mouse [33]. On this basis, CECs and CEPs are promising potential biomarkers for antiangiogenetic therapy, particularly for ramucirumab, so further evaluation is warranted.